title: Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology.
abstract: BACKGROUND
  Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assistance has not been determined. Furthermore, it is unclear whether the effects of partial ventilatory support depend on acute lung injury (ALI) etiology. This study aimed to investigate the impact of spontaneous and time-cycled control breaths during BIVENT on the lung and diaphragm in experimental pulmonary (p) and extrapulmonary (exp) ALI.
  
  
  METHODS
  This was a prospective, randomized, controlled experimental study of 60 adult male Wistar rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALI(p)) or intraperitoneally (ALI(exp)). After 24 hours, animals were anesthetized and further randomized as follows: (1) pressure-controlled ventilation (PCV) with tidal volume (V(t)) = 6 ml/kg, respiratory rate = 100 breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75, and 50 breaths/min). BIVENT was set with two levels of CPAP (P(high) = 10 cmH2O and P(low) = 5 cmH2O). Inspiratory time was kept constant (T(high) = 0.3 s).
  
  
  RESULTS
  BIVENT was associated with reduced markers of inflammation, apoptosis, fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both ALI models when compared to PCV. The inspiratory effort during spontaneous breaths increased during BIVENT-50 in both ALI models. In ALI(p), alveolar collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and diaphragmatic injury was lower during BIVENT-50 compared to PCV and BIVENT-100. In ALI(exp), alveolar collapse during BIVENT-100 and BIVENT-75 was comparable to PCV, while decreasing with BIVENT-50, and diaphragmatic injury increased during BIVENT-50.
  
  
  CONCLUSIONS
  In mild ALI, BIVENT had a lower biological impact on lung tissue compared to PCV. In contrast, the response of atelectasis and diaphragmatic injury to BIVENT differed according to the rate of spontaneous/controlled breaths and ALI etiology.
authors.forename: Felipe
authors.initials: F
authors.lastname: Saddy
authors.forename: Lillian
authors.initials: L
authors.lastname: Moraes
authors.forename: Cintia Lourenço
authors.initials: CL
authors.lastname: Santos
authors.forename: Gisele Pena
authors.initials: GP
authors.lastname: Oliveira
authors.forename: Fernanda Ferreira
authors.initials: FF
authors.lastname: Cruz
authors.forename: Marcelo Marcos
authors.initials: MM
authors.lastname: Morales
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Marcelo Gama
authors.initials: MG
authors.lastname: de Abreu
authors.forename: Cristiane Souza Nascimento Baez
authors.initials: CS
authors.lastname: Garcia
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Patricia Rieken Macêdo
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D001938:Brazil; D004195:Disease Models, Animal; D004727:Endothelium / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005355:Fibrosis; D001239:Inhalation / Q000502:physiology; D007385:Intermittent Positive-Pressure Ventilation / Q000009:adverse effects / Q000379:methods*; D008168:Lung / Q000473:pathology*; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013990:Tidal Volume / Q000502:physiology
chemical_list: D015415:Biomarkers